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Mediators of Inflammation
Volume 2015 (2015), Article ID 614518, 9 pages
Research Article

Origin of Circulating Free DNA in Sepsis: Analysis of the CLP Mouse Model

1Division of Infection Control and Prevention, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
2International Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan
3Department of Clinical Epidemiology and Biostatistics, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
4Infectious Disease Surveillance Center, National Institute of Infectious Diseases, Tokyo 162-8640, Japan

Received 25 September 2014; Revised 2 January 2015; Accepted 20 January 2015

Academic Editor: Mashkoor A. Choudhry

Copyright © 2015 Shigeto Hamaguchi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Recently, it has been reported that circulating free DNA (cf-DNA) in the blood is increased in various infectious diseases, including sepsis. Moreover, a relationship between cf-DNA and neutrophil extracellular traps (NETs) has been suggested. However, it is still unclear what the source and physiological role of cf-DNA in sepsis are. In this study, we examined the source of cf-DNA by detecting citrullinated histone H3, a characteristic feature of NET formation, in cecal ligation and puncture- (CLP-)operated mice. In addition, neutrophil depletion using anti-Ly6G antibodies was performed to assess the association between neutrophils and cf-DNA. Increased cf-DNA levels were observed only in CLP mice and not in the control groups; the qPCR findings revealed that the cf-DNA was mainly host-derived, even in bacteremic conditions. Citrullinated histone H3 was not increased in the neutrophils upon CLP, and the depletion of neutrophils showed limited effects on decreasing the amount of cf-DNA. Taken together, these results suggested that elevated cf-DNA levels during early-phase sepsis may represent a candidate biomarker for the severity of sepsis and that, contrary to previous findings, cf-DNA is not derived from neutrophils or NETs.